This invention concerns a process for the manufacture of anhydro- and dianhydro- hexitols, pentitols, and tetritols by the dehydration of sugar alcohols (alditols) in the presence of a dehydration catalyst and with the assistance of an inert gas sparge.
Anhydro sugar alcohols, in particular derivatives of mannitol, iditol, and sorbitol, are known for their therapeutic uses and uses in food. At least one of these, isosorbide, 1,4:3,6-dianhydrosorbitol, is a monomer useful in the manufacture of polymers and copolymers, especially polyester polymers and copolymers. Isosorbide is a derivative of sorbitol, which can be derived from various natural resources. Sorbitol may be regarded as a renewable natural resource for the manufacture of polymers.
Anhydrosugar alcohols are known to be produced by dehydration of the corresponding sugar alcohols (or monoanhydro sugar alcohols) by the action of various dehydration catalysts, typically strong acids. Examples of these catalysts include sulfonated polystyrenes (H+form) (German Patent DE 3 041 673 C2; Canadian Patent Disclosure CA 1 178 288 A1); and various mineral acids, such as HCl (U.S. Pat. No. 4,169,152; German Patent Disclosure DE 3 233 086 A1), H3PO4 (East German Patent Disclosure DD 1 32 266; Can. J. Chem., 52 (19) 3362-72 (1974)), HF (International Patent Disclosure WO 89/00162 A; Carbohydr. Res. 205 (1990) 191-202) and H2SO4 (German Patent Disclosures DE 3 521 809 A1 and DE 3 229 412 A1).
These processes are often performed in the presence of a solvent. As solvents, water (CA 1 178 288 A1; European Patent Disclosure EP 0 052 295 B1) and organic solvents such as toluene or xylene (Przem. Chem. 48 (11) 665-8 (1969)) are known.
Batch processes for the preparation of dianhydro sugar alcohols by acid dehydration have been described in numerous patents and articles, for example, U.S. Pat. No. 3,454,603; 4,564,692; and 4,506,086; Canadian Patent 1178288; and articles J. Am. Chem. Soc., 68(5) pp. 939-941 (1946); J. Chem. Soc., pp. 433-436 (1947); Przem. Chem. 48(11) pp. 665-668 (1969); and Pr. Nauk. Inst. Technol. Org. Tworzyw Sztucznych Politech. Wroclaw. No 3., p. 3-14 (1971).
In particular, a batch process for the formation of the dianhydro sugar alcohol isosorbide has been described in the literature as a two step process involving intramolecular dehydration of sorbitol to sorbitan (1,4-monoanhydro-sorbitol), and further reaction of sorbitan to isosorbide (1,4:3,6-dianhydrosorbitol) in an acid catalyzed dehydration-cyclization. In this process, an aqueous solution of sorbitol is charged to a batch reactor. The temperature is increased to 130xc2x0 C.-135xc2x0 C. under vacuum (35 mm Hg) to remove the water. When the sorbitol melt is free of water, a catalyst, usually sulfuric acid, is added and the temperature and vacuum levels are maintained. The operable temperature range of the reaction is very narrow. Higher temperatures lead to decomposition and charring of the end product, while lower temperatures inhibit the reaction rate due to difficulties in removal of the water of reaction. This reaction produces isosorbide and a higher molecular weight by-product. The by-product is presumably produced in part by water elimination between two or more sorbitol molecules, but its exact nature is not clearly defined. See Starch/Starke (1986), 38(c), 26-30 and Roland Beck, Pharm. Mfg Inc. (1996), 97-100. Other monoanhydro by-products, 2,5-anhydro-L-iditol and 2,5-anhydro-D-mannitol, are also known to be produced under some reaction conditions. (Acta. Chem. Scand. B 35, 441-449 (1981)).
International Patent Application WO 00/14081 describes a continuous process for producing anhydro sugar alcohols, especially isosorbide, comprising the steps of introducing at least one sugar alcohol or monoanhydro sugar alcohol into a reaction vessel; dehydrating the sugar alcohol or monoanhydro sugar alcohol in the presence of an acid catalyst and an organic solvent to form a reaction product which is at least partly soluble in the organic solvent; removing water from the reaction vessel; removing organic solvent comprising the dissolved reaction product from the reaction vessel; separating the reaction product from the removed organic solvent; and recycling the organic solvent into the reaction vessel.
It is an object of the present invention to provide an improved process for the manufacture of anhydro sugar alcohols, especially isosorbide, by the acid catalyzed dehydration of sugar alcohols that facilitates large scale, economical production without the use of vacuum. One of the salient features of the present invention is the use of an inert gas purge which removes water from the reaction mixture, thereby accelerating the rate of reaction.
Disclosed is a process for the preparation of a dianhydro sugar alcohol comprising the steps of:
a) introducing to a single vessel a charge of at least one sugar alcohol or monoanhydro sugar alcohol, and optionally, water and, optionally, a dehydration catalyst;
b) contacting said charge with a flow of an inert gas at elevated temperature to remove the bulk of any water present to yield a dewatered process charge;
c) contacting said dewatered process charge with a dehydration catalyst in the presence of a flow of an inert gas at elevated temperatures so as to remove water of reaction as formed.
Disclosed is an apparatus for conducting said process which apparatus comprises a vessel containing a tube which allows the flow of nitrogen through the sorbitol under the conditions of the process. A trap is provided to trap volatilized isosorbide carried with the nitrogen flow.